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目的建立液相色谱-质谱(LC-MS)法测定Beagle犬血浆N-去二甲基西布曲明浓度,并用于药动学研究。方法6条Beagle犬随机分成2组,采用自身对照交叉实验设计,分别单次口服盐酸西布曲明胶囊(参比制剂)和自制盐酸西布曲明固体分散体(受试制剂)各2.5 mg,以地西泮为内标,采用Phenomenex-Lunal00-3 C_(18)色谱柱,流动相为甲醇-4 mmol·L~(-1)乙酸铵-甲酸(70.5:29:0.5,V:V:V),电喷雾正离子选择反应监测,测定血药浓度。结果受试制剂与参比制剂的代谢物N-去二甲基西布曲明的c_(max)分别为(7.8±s 1.2)和(7.4±1.3)μg·L~(-1),t_(max)分别为(4.2±0.9)和(4.6±0.8)h,t_(1/2)分别为(21±3)和(20.1±2.7)h,AUC_(0～∞)分别为(179±46)和(169±43)μg·h·L~(-1),与参比制剂相比受试制剂的相对生物利用度为(105±14)%。结论该方法快速、准确,适用于N-去二甲基盐酸西布曲明在Beagle犬体内的药动学研究,主要药动学参数经方差分析和双向单侧t检验证明,2种制剂生物等效。
Objective To establish a liquid chromatography-mass spectrometry (LC-MS) method for the determination of plasma N-desmethylbuterib concentration in Beagle dogs and to study the pharmacokinetics. Methods Six Beagle dogs were randomly divided into two groups. The self-controlled crossover experimental design was adopted. Single oral sibutramine hydrochloride capsules (reference preparation) and homemade sibutramine hydrochloride solid dispersion (test preparation) 2.5 mg , And the mobile phase was Phenomenex-LIBA 300-3 C 18 with the mobile phase of 4 mmol·L -1 ammonium acetate-formic acid (70.5: 29: 0.5, V: V : V), electrospray positive ion selective reaction monitoring, determination of plasma concentration. Results The cmax of the metabolite N-desmethylbupoomarin were (7.8 ± s 1.2) and (7.4 ± 1.3) μg · L -1, t_ (max) were (4.2 ± 0.9) and (4.6 ± 0.8) h, t 1/2 was 21 ± 3 and 20.1 ± 2.7 h respectively, and AUC 0 ~ ∞ were respectively 179 ± 46) and (169 ± 43) μg · h · L -1, respectively. The relative bioavailability of the test preparation was (105 ± 14)% compared with the reference formulation. Conclusions This method is rapid and accurate and is suitable for the pharmacokinetics study of sibutramine hydrochloride in beagle dogs. The main pharmacokinetic parameters were analyzed by ANOVA and two-way unilateral t-test. Equivalent.